Mental illness encompasses both psychoses and neuroses. Symptoms requiring treatment include depression, anxiety, agitation, and hallucinations. Among the drugs used particularly for treatment of both reactive and endogenous depressions are monoamine oxidase (MAO) inhibitors, such as iproniazide, tranylcypromine, nialamide, phenelzine, and pargyline, and the non-MAO-inhibiting tricyclic aromatic dibenzazepines, such as imipramine, and dibenzocycloheptanes such as amitriptyline.
All of these drugs have adverse side effects that limit their usefulness. MAO inhibitors may benefit milder forms of depression, but the risk of serious toxic effects is a strong argument against their use. They may cause liver damage and acute hypertension, especially if given in conjunction with cheese, bananas, or other amine-containing foods. The MAO inhibitors may also cause tremors, insomnia, hyperhydrosis, agitation, hypermanic behaviour, confusion, hallucinations, convulsions and orthostatic hypotension. They frequently cause dizziness, vertigo, headache, inhibition of ejaculation, difficulty in urination, weakness, fatigue, dry mouth, constipation and blurred vision.
Imipramine may cause blurred vision, dryness of mouth, constipation, urinary retention, orthostatic hypotension, respiration depression, myocardial infarction, and congestive heart failure. Similar difficulties are experienced with amitriptyline.
There is a continuing need for psychotherapeutic agents that have fewer side effects than the drugs in use today; also for psychotherapeutic agents that have different modes of action than presently used agents, since none of these is completely effective.
British Patent Specification No. 888,657 and Canadian Pat. No. 1,079,734 disclose piperidinecarbinols, useful as analgesics and cough suppressants, of the formula ##STR2## wherein X is phenyl;
Y is hydroxymethyl, 1-hydroxymethyl or 1-hydroxypropyl; PA1 alk is alkylene of up to six carbon atoms; PA1 R is an oxygen- or nitrogen-containing heterocyclic group, tetrahydrofurfuryloxyethyl, aryl, aryloxy, aralkoxy, alkoxy of up to six carbon atoms or alkoxy substituted by hydroxy, ethoxy or phenoxy. PA1 (b) each of R.sup.2 and R.sup.3 is independently selected from H and lower alkyl of 1 to 4 carbon atoms; R.sup.1 and R.sup.2 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 or 4 carbon atoms; or R.sup.2 and R.sup.3 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 to 6 carbon atoms; PA1 (c) R.sup.4 is PA1 (d) each of R.sup.5 and R.sup.6 is independently selected from alkyl of 1 to 12 carbon atoms and cycloalkyl of 3 to 8 carbon atoms or R.sup.5 and R.sup.6 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 to 11 carbon atoms, PA1 (1) R.sup.4 Br is lithiated with n-butyllithium to produce R.sup.4 Li which is then reacted with the piperidinone of the formula: ##STR6## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above,
and
Compounds of such structure wherein Y is alkanoyl and the other substituents are similarly defined are also known from British Patent Specification No. 841,120.
Kagi et al., Helvetica Chimica Acta, Vol. XXXII, 2489 (1949) disclose the synthesis of various analgesics; intermediate compounds of the formula ##STR3## wherein R.sub.2 is CH.sub.3 or n-C.sub.3 H.sub.7 are disclosed.
Lewis et al., J. Chem. Soc. C., 1970, 1074, disclose compounds of the formula ##STR4##